Transmission electron microscopes (TEM) use a TEM grid to support specimens during imaging in the electron microscope, much as glass slides are used in light microscopes. TEM grids, generally referred to only as “grids,” are also occasionally used in other applications. Standard TEM grids are 3.05 mm diameter disks of fine-mesh screen-like material, and are very thin, typically 30 μm to 100 μm thick. Most commonly, grids are made from, but are not limited to, Cu, Ni, Au, or NiCr alloy, but may also be made from other metals or for some applications may be polymeric, ceramic (e.g. silicon), or of special materials such as pyrolytic carbon, or still other materials. Some of the special grid materials can be thicker, such as about 200 μm thick for pyrolytic carbon.
Due to the need for grids to be very thin and for the screen to be a very open mesh, since it is through the openings that specimens are imaged, TEM grids are extremely fragile and easily damaged. Due to their small size, grids are very easy to lose if dropped or misplaced. Also, due to their very small size, it is not generally possible to mark or label individual grids to identify the specimen attached to them. Therefore, the identification of a grid, and the specimen it holds, is dependant on it being in a properly labeled location or container. Proper identification is essential when grids contain specimens from clinical patients, such as biopsies, or important research materials. Preparation of a grid with a specimen can often take several days of labor; hence loss or misidentification is very expensive in terms of time and effort.
Numerous types of storage containers are used to store grids. There are similarly also many devices used to treat the specimens on the grids. Both the storage devices and many of the processing devices, especially those that are intended to hold more than one grid at a time, provide indexed positions for individual grids. A device having multiple indexed locations to place grids for storage is called a grid box. Processing of grids commonly includes chemical stains or molecular labels to enable detection and localization of specific biological, structural, or chemical features. For biological specimens, especially, many solutions of stains and other chemicals are applied to the grid in liquids such as, but not limited to, water. Alternatively, in some processes, typically for non-biologic specimens, the stain or treatment may be applied as a vapor. In still others, the treatment, such as with ionized materials, may occur in a partial vacuum.
In many clinical or research labs it is not uncommon to need to process 10, 20, 30, or more grids at a time. Hence, devices that can perform simultaneous processing are desirable. Since many of the staining regents are toxic and/or are expensive, it is also desirable to minimize the consumption of these reagents.
All storage and processing devices require a means to hold and retain the grid in an identified indexed location. There are many devices and methods to hold grids in current use, for both storage and processing. In all current or conventional devices, the grid must be transferred from a storage device to a processing device or devices, and then back to a storage device. Additionally, in current or conventional devices, the grid must also be removed from the storage device and placed into the electron microscope for imaging. The major types of conventional grid holding devices are listed below. Also, briefly discussed are the principal limitations of these devices:    1. Referring now to FIGS. 1 and 2, a conventional Prior Art grid holder 100 is shown that is configured to hold a grid 1 for storage or processing entraps the grid in a slot. Conventional grid holders similar to grid holder 100 may be configured to include a single slot or a plurality of slots, with each slot configured to receive a single grid. The grid is conventionally enclosed on all except one side. Grids are conventionally held loose within slots 2, as shown in FIGS. 1 and 2. Most commonly the slot has a diamond or trapezoidal shape as viewed from the top that minimizes the contact of the grid faces with the wall of the slot, in order to avoid possible damage to the specimen, as shown in FIG. 1. The slot is conventionally rectangularly shaped when viewed from the side as shown in FIG. 2. To entrap a grid, the top of the slot may be closed with a close fitting sliding or rotating lid. In devices having multiple slots for receiving grids, the lid may be designed such that only a few grid slots are open at any time and not the whole holder. Such a lid is not shown in FIGS. 1 and 2.            a. Most grid boxes used for grid storage are opened with a sliding or rotating lid. When these are opened to access the grids, the loosely held grids sometimes pop out. This may occur due to static charge attraction or repulsion, or simply due to minimal mechanical jarring or jostling by the user. At times, more then one grid may pop out, and these grids may then become mixed up, so that identity is not clear. Even when a grid box is closed, grids can sometimes slip out of their slot since they are so thin, and then the grid may fall into a nearby slot. Thus, once again, the identity of the grid is not clear. This especially occurs when grid boxes are jostled, such as in routine transport; or it can occur due to static charge attraction of the grid to the grid box lid.        b. On occasion, conventional grid holders or grid processing holders of a similar configuration may be used to stain or process grids. When grids are stained or otherwise processed within such devices, generally with a liquid or sometimes a gas or vapor, the stain or other treating agent has limited circulation to the grid since flow is restricted due to the absence of flow-through circulation. Thus staining or other treatment often is uneven.            2. Some devices clamp grids with elastomeric polymer clamps. These are typically used for holding grids to enable immersion in staining solutions. Typically these are simply thin slits cut into an elastomeric material such as silicone rubber, polyurethane, or plasticized polyvinylchloride. The grid is then partially inserted so as to have the clamping action hold the grid by its edge. This is not shown in the figures.            a. The elastomeric clamping action can wear out, and is not always very secure. Chemical treatments with solvents and oxidizing reagents, commonly used in specimen preparation, can also cause elastomeric materials to break down and hence these devices can lose tension and thence release the grid.        b. With many designs it is easy to accidently clamp onto the more central portions of the grid and hence damage the specimen that is located in the center region.            3. Forceps are commonly used to temporarily hold grids by clamping, preferably, onto the edge of a grid. Such forceps handing is used to move grids from one solution to another for processing. A common procedure is for users to place droplets of staining solution on a hydrophobic material (so that the droplets bead up) and then transfer the grids from droplet to droplet.            a. It is difficult to handle multiple grids with forceps. In practice it is not uncommon to need to process a dozen or more grids at a time with droplet staining (or similar procedures). Such handling requires substantial practice and is very tedious, especially for those with less than perfect eyesight and/or coordination. Consequently, mix-ups and damage are always a concern and often a problem.            4. Magnetic holders are used in some devices wherein the grid is held in place with magnetic attraction.            a. These devices are limited to use with paramagnetic grids, such as those made from NiCr alloys. However, this excludes the most common grids in use that are made from copper, and many other non-magnetic grid materials, thereby limiting the broad utility of such devices.        b. Typically the magnetic holder is designed such that it contacts one entire side or face, or the majority of one side or face of the grid. Thus, if the grid is placed onto the holder in the wrong orientation the specimen may be damaged. Since specimens are ultrathin and often invisible to the naked eye, it is often difficult to know on which side the specimen is held.            5. Adhesives are used in some devices to hold grids. With one such device, the grids are stuck onto a stick that is inserted into liquids for processing.            a. In practice, the adhesives have a limited useful lifetime.        b. The adhesive may be affected by processing chemicals, such as solvents and oxidants, such that the adhesive can fail during use.        c. Non-standard especially thick and stronger grids are recommended to prevent bending of the grid when removing from the adhesive coated device substrate. This limits the type of grids that may be used. Moreover, such thick grids are not desirable in some applications, such as tomographic imaging.            6. Grids are held by circular clamps or retaining rings after insertion into counter-bored holes in devices such as electron microscopes and various other instruments, such as vacuum instruments.            a. These types of holders are very secure and may be designed to hold the grid flat for imaging. However, such grid holding devices are typically machined from high quality metal alloys and require complex manufacturing to produce. Thus, these are too expensive for use in storage containers and in many processing devices. These are generally only used in electron microscopes and some devices used to prepare specimens that require a vacuum.        